A transarterial embolization treatment has been currently employed for the treatment of liver cancer, fibroid, kidney cancer and the like. The treatment method is based on the mechanism in which an anti-cancer agent is injected into a cancer (myoma) tissue using a microcatheter, the blood vessels reaching the cancer (myoma) tissue are blocked with an embolic material while using a non-ionic contrast agent, whereby supply of nutrition to the cancer (myoma) is shut off to cause necrosis of the cancer (myoma). This treatment method is a tissue-selective treatment method which can minimize the side effects of necrosis of normal cells. With the recent progress of the medical technique, there is a demand for embolic materials having a particle size ranging from as small as 40 μm to as large as 2000 μm, which have a uniform particle size and a uniform shape, so that the blood vessels can be embolized at positions as close as possible to the target site to avoid an adverse influence on the healthy part, and a material suitable for the size of the blood vessels can be selected.
JP-B-3879018 discloses a production method of particles by a dispersion in liquid method. To be precise, a biocompatible substance is dissolved in a good solvent and the solution is added to a poor solvent for the biocompatible substance and stirred to give an emulsion. Then, the obtained emulsion is cooled to a temperature not higher than the gelling temperature of the biocompatible substance to form gel particles. The particles of the biocompatible substance are obtained from the thus-obtained gel particles. In addition, JP-B-1-17376 describes a production method of spherical gelatin particles by a dispensing in liquid method. To be precise, a nozzle is immersed in a hydrophobic solvent, the nozzle opening is reciprocated in the horizontal direction (pendular motion), and a gelatin solution is press-discharged from the nozzle tube into the hydrophobic solvent at a temperature not lower than the gelling temperature.
As a method of producing gelatin particles, the conventionally-employed dispersion in liquid method is shown in FIG. 1. According to the dispersion in liquid method, an aqueous gelatin solution 11 is fed into a hydrophobic solvent bath (hereinafter solvent bath) 16 containing a hydrophobic solvent 12 such as oil and the like (FIG. 1A), and the mixture is stirred or dispersed with an agitating blade 13 to give an aqueous gelatin solution droplet 14 (FIG. 1B), then the solvent bath 16 is cooled with cold water 15 and the like (FIG. 1C). While the dispersion in liquid method is convenient, since the particle size distribution of the obtained particles is very wide, from about a few μm to about a few thousand μm, the yield of gelatin particles having desired particle sizes becomes considerably low. What is more, complete classification is not available due to coagulation of substances even after a classification operation and the like. Thus, the method is not suitable for the production of microparticles such as granules and the like.
On the other hand, the dispensing in liquid method described in JP-B-1-17376 improves the problem in conventional dispensing in liquid method which requires a cutting means of gelatin solution in a hydrophobic solvent. However, in the method described in patent document 2 including horizontal movement of a nozzle, the droplets discharged from the nozzle are not easily detached therefrom, and the method was insufficient to stably produce 40-2000 μm gelatin particles.